Higher CD4+ T Cell Counts Associated with Low Viral pol Replication Capacity among Treatment-Naive Adults in Early HIV-1 Infection

• Published in: The Journal of infectious diseases 2004-07, Vol.190 (2), p.251-256
• Main Authors: Barbour, Jason D, Hecht, Frederick M, Wrin, Terri, Segal, Mark R, Ramstead, Clarissa A, Liegler, Teri J, Bursch, Michael P, Petropoulos, Christos J, Hellmann, Nicholas S, Kahn, James O, Grant, Robert M
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - pharmacology; Biological and medical sciences; CD4 Lymphocyte Count; Drug Resistance, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Products, pol - metabolism; HIV Infections - immunology; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - pathogenicity; HIV-1 - physiology; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Miscellaneous; RNA, Viral - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Virulence; Virus Replication
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/422036

Background. Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4+ T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity (RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs. Methods. Virus replication over a single cycle was measured by use of a viral test vector containing patient derived HIV-1 protease and reverse transcriptase gene segments. Results. Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (⩽43% of the reference virus) had significantly higher CD4+ T cell counts at study entry, independent of drug resistance and plasma HIV-1 RNA level, and over time, both before and during combination antiretroviral therapy. Conclusions. Viral pol RC may influence HIV-1 disease progression by affecting the amount and tissue distribution of viral replication. The pol RC value of 43% may represent a threshold below which HIV-1 has lowered virulence and is less able to deplete CD4+ T cell counts.